To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible (MSSA) bacteremia.

A literature search using the PubMed database (inception to December 2022) was conducted using the search terms " bacteremia," "methicillin-susceptible bacteremia," "persistent methicillin-susceptible bacteremia," and "refractory methicillin-susceptible bacteremia ." In addition, therapeutic agents which could be used as treatment for MSSA including "nafcillin," "oxacillin," "cefazolin," "ceftaroline," "gentamicin," "rifampin," and "daptomycin" were also combined with the aforementioned search terms to capture data using these agents.

Clinical data were limited to those published in the English language. Articles and abstracts were considered for inclusion in addition to ongoing trials identified through ClinicalTrials.gov.

A total of 78 articles were reviewed including 17 in vitro or animal model studies and 39 studies including patient data. The remaining 22 articles included guidelines, review articles, and editorials. Recent data evaluating use of dual β-lactam regimens for persistent MSSA bacteremia were limited to 8 case reports or case series.

At present, there is little guidance on how to best manage patients with persistent MSSA bacteremia. This narrative review collates the available data to assist clinicians in selecting the best possible antimicrobial regimen when facing this clinical conundrum.

Modification of antimicrobial therapy, in conjunction with source control and infectious diseases consultation, may all be necessary to sterilize blood cultures in patients with persistent MSSA bacteremia.